IV or IV/PO Omadacycline vs. IV/PO Levofloxacin for the Treatment of Acute Pyelonephritis

• ClinicalTrials.gov Identifier: NCT03757234
• Recruitment Status: Completed
• First Posted: November 28, 2018
• Results First Posted: July 7, 2020
• Last Update Posted: July 7, 2020
• Sponsor: Paratek Pharmaceuticals Inc
• Information provided by (Responsible Party): Paratek Pharmaceuticals Inc

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Acute Pyelonephritis
• Interventions: Drug: Omadacycline; Drug: Levofloxacin
• Enrollment: 201

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Omadacycline 200 iv/200 iv	Omadacycline 200 iv/100 iv	Omadacycline 200 iv/300 po or 100 iv	Omadacycline 200 iv/450 po or 100 iv	Levofloxacin 750 iv/750 po or iv
Arm/Group Description	On Day 1, participants received omadacycline 200 milligrams intravenously (iv). On Days 2 through 7, participants continued to receive omadacycline 200 milligrams iv. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes.	On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes.	On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv or omadacycline 300 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.	On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv or omadacycline 450 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.	On Day 1, participants received levofloxacin 750 milligrams iv. On Days 2 through 7, participants received levofloxacin 750 milligrams iv or levofloxacin 750 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.
Period Title: Overall Study
Started	75	18	17	17	74
Completed PTE Visit	72	16	17	16	71
Completed	72	16	17	16	70
Not Completed	3	2	0	1	4
Reason Not Completed
Adverse Event	0	0	0	0	1
Lost to Follow-up	1	0	0	0	1
Withdrawal by Subject	1	1	0	1	2
Other	1	1	0	0	0

Baseline Characteristics

Arm/Group Title		Omadacycline 200 iv/200 iv	Omadacycline 200 iv/100 iv	Omadacycline 200 iv/300 po or 100 iv	Omadacycline 200 iv/450 po or 100 iv	Levofloxacin 750 iv/750 po or iv	Total
Arm/Group Description		On Day 1, participants received omadacycline 200 milligrams intravenously (iv). On Days 2 through 7, participants continued to receive omadacycline 200 milligrams iv. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes.	On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes.	On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv or omadacycline 300 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.	On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv or omadacycline 450 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.	On Day 1, participants received levofloxacin 750 milligrams iv. On Days 2 through 7, participants received levofloxacin 750 milligrams iv or levofloxacin 750 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.	Total of all reporting groups
Overall Number of Baseline Participants		75	18	17	17	74	201
Baseline Analysis Population Description		The intent-to-treat (ITT) population consisted of all randomized participants regardless of whether or not the participant received study drug.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	75 participants	18 participants	17 participants	17 participants	74 participants	201 participants
		38.2 (14.97)	33.9 (14.48)	37.1 (15.97)	38.2 (17.66)	38.8 (14.74)	37.9 (15.07)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	75 participants	18 participants	17 participants	17 participants	74 participants	201 participants
	Female	75 100.0%	18 100.0%	17 100.0%	17 100.0%	74 100.0%	201 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	75 participants	18 participants	17 participants	17 participants	74 participants	201 participants
	Hispanic or Latino	1 1.3%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 0.5%
	Not Hispanic or Latino	74 98.7%	18 100.0%	17 100.0%	17 100.0%	74 100.0%	200 99.5%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	75 participants	18 participants	17 participants	17 participants	74 participants	201 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	1 1.3%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 0.5%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	White	74 98.7%	18 100.0%	17 100.0%	17 100.0%	74 100.0%	200 99.5%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With an Investigator Assessment of Clinical Response at the Post Therapy Evaluation (PTE) Visit (ITT Population)
Description	Clinical response was determined by the investigator at the PTE visit by assessing whether or not the participant met the clinical outcome of Clinical Success, Clinical Failure, or Indeterminate. Clinical Success was defined as the complete resolution or significant improvement of the baseline AP signs and symptoms at the PTE visit such that no additional antimicrobial therapy is required for the current infection. Clinical Failure was defined as no apparent response to therapy or persistence of signs and symptoms of infection or reappearance of signs and symptoms at or before the PTE visit such that use of additional systemic antimicrobial therapy for the current infection was required or death at or before the PTE visit. The clinical outcome was deemed as Indeterminate when the PTE visit was not completed.
Time Frame	Day 21 (A PTE occurred on Day 21 ± 2 days after the participant's first dose of study drug).

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population consisted of all randomized participants regardless of whether or not the participant received study drug.

Arm/Group Title	Omadacycline 200 iv/200 iv	Omadacycline 200 iv/100 iv	Omadacycline 200 iv/300 po or 100 iv	Omadacycline 200 iv/450 po or 100 iv	Levofloxacin 750 iv/750 po or iv
Arm/Group Description:	On Day 1, participants received omadacycline 200 milligrams intravenously (iv). On Days 2 through 7, participants continued to receive omadacycline 200 milligrams iv. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes.	On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes.	On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv or omadacycline 300 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.	On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv or omadacycline 450 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.	On Day 1, participants received levofloxacin 750 milligrams iv. On Days 2 through 7, participants received levofloxacin 750 milligrams iv or levofloxacin 750 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.
Overall Number of Participants Analyzed	75	18	17	17	74
Measure Type: Count of Participants; Unit of Measure: Participants
Clinical Success	68 90.7%	15 83.3%	15 88.2%	16 94.1%	69 93.2%
Clinical Failure	5 6.7%	1 5.6%	2 11.8%	0 0.0%	1 1.4%
Indeterminate	2 2.7%	2 11.1%	0 0.0%	1 5.9%	4 5.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 200 iv/200 iv, Levofloxacin 750 iv/750 po or iv
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-2.6
	Confidence Interval	(2-Sided) 95%; -12.4 to 6.9
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from levofloxacin (omadacycline minus levofloxacin) in clinical success rate was estimated.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 200 iv/100 iv, Levofloxacin 750 iv/750 po or iv
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-9.9
	Confidence Interval	(2-Sided) 95%; -34.8 to 5.3
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from levofloxacin (omadacycline minus levofloxacin) in clinical success rate was estimated.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 200 iv/300 po or 100 iv, Levofloxacin 750 iv/750 po or iv
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-5.0
	Confidence Interval	(2-Sided) 95%; -30.6 to 8.2
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from levofloxacin (omadacycline minus levofloxacin) in clinical success rate was estimated.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 200 iv/450 po or 100 iv, Levofloxacin 750 iv/750 po or iv
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 95%; -22.4 to 11.8
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from levofloxacin (omadacycline minus levofloxacin) in clinical success rate was estimated.

2. Primary Outcome

Title	Number of Participants With a Microbiological Response at the PTE Visit (Micro-ITT Population)
Description	Microbiological response was determined programmatically at the PTE visit by assessing whether or not the participant met the microbiological outcome of 'Success', 'Failure', or 'Indeterminate'. Participants were considered to have a microbiological response of 'Success' if the outcomes of each baseline pathogens were eradication at the PTE visit. Participants were considered to have a microbiological response of 'Failure' if the outcome for any pathogen was persistence. Participants were considered to have a microbiological response of 'Indeterminate', if the outcome of at least 1 baseline pathogen was indeterminate and there was no outcome of persistence for any baseline pathogen.
Time Frame	Day 21 (A PTE occurred on Day 21 ± 2 days after the participant's first dose of study drug).

Outcome Measure Data

Analysis Population Description

The micro-ITT population consisted of participants in the ITT population who had an appropriately collected pretreatment baseline urine culture with at least 1 uropathogen at ≥10^5 colony forming unit (CFU)/mL and not more than 2 bacterial isolates at any colony count.

Arm/Group Title	Omadacycline 200 iv/200 iv	Omadacycline 200 iv/100 iv	Omadacycline 200 iv/300 po or 100 iv	Omadacycline 200 iv/450 po or 100 iv	Levofloxacin 750 iv/750 po or iv
Arm/Group Description:	On Day 1, participants received omadacycline 200 milligrams intravenously (iv). On Days 2 through 7, participants continued to receive omadacycline 200 milligrams iv. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes.	On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes.	On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv or omadacycline 300 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.	On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv or omadacycline 450 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.	On Day 1, participants received levofloxacin 750 milligrams iv. On Days 2 through 7, participants received levofloxacin 750 milligrams iv or levofloxacin 750 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.
Overall Number of Participants Analyzed	46	11	14	13	52
Measure Type: Count of Participants; Unit of Measure: Participants
Clinical Success	32 69.6%	3 27.3%	9 64.3%	5 38.5%	39 75.0%
Clinical Failure	13 28.3%	7 63.6%	5 35.7%	7 53.8%	11 21.2%
Indeterminate	1 2.2%	1 9.1%	0 0.0%	1 7.7%	2 3.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 200 iv/200 iv, Levofloxacin 750 iv/750 po or iv
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-5.4
	Confidence Interval	(2-Sided) 95%; -23.6 to 12.7
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from levofloxacin (omadacycline minus levofloxacin) in clinical success rate was estimated.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 200 iv/100 iv, Levofloxacin 750 iv/750 po or iv
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-47.7
	Confidence Interval	(2-Sided) 95%; -71.3 to -6.0
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from levofloxacin (omadacycline minus levofloxacin) in clinical success rate was estimated.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 200 iv/300 po or 100 iv, Levofloxacin 750 iv/750 po or iv
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-10.7
	Confidence Interval	(2-Sided) 95%; -40.8 to 15.1
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from levofloxacin (omadacycline minus levofloxacin) in clinical success rate was estimated.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 200 iv/450 po or 100 iv, Levofloxacin 750 iv/750 po or iv
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-36.5
	Confidence Interval	(2-Sided) 95%; -62.6 to -1.1
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from levofloxacin (omadacycline minus levofloxacin) in clinical success rate was estimated.

3. Primary Outcome

Title	Number of Participants With Resolution of All AP Signs and Clinical Symptoms at PTE Visit (ITT Population)
Description	Participants recorded their assessments using the Modified Patient Symptom Assessment Questionnaire (mPSAQ), a 6-item questionnaire that assessed the levels of 'severity' and 'bothersomeness' for six pyelonephritis signs and symptoms. The sub-scale responses were recorded as 'did not have', 'mild', 'moderate', and 'severe' for 'severity'; and 'not at all', 'a little', 'moderately', and 'a lot' for 'bothersomeness', both scored 0-3. Total scores were calculated by summing the non-missing scores of the 6 items, divided by the number of non-missing items, and then multiplied by 6. For each sub-scale, the total score ranged from 0 (least Severe/ least bothersome) and 18 (worst severity/most bothersome). Number of participants with resolution of all symptoms, without occurrence of new symptoms is reported. Resolution was defined as absence of all baseline symptoms.
Time Frame	Day 21 (A PTE occurred on Day 21 ± 2 days after the participant's first dose of study drug).

Outcome Measure Data

Analysis Population Description

The ITT population consisted of all randomized participants regardless of whether or not the participant received study drug. Participants who completed the PTE visit with evaluable data were analyzed for this end point.

Arm/Group Title	Omadacycline 200 iv/200 iv	Omadacycline 200 iv/100 iv	Omadacycline 200 iv/300 po or 100 iv	Omadacycline 200 iv/450 po or 100 iv	Levofloxacin 750 iv/750 po or iv
Arm/Group Description:	On Day 1, participants received omadacycline 200 milligrams intravenously (iv). On Days 2 through 7, participants continued to receive omadacycline 200 milligrams iv. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes.	On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes.	On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv or omadacycline 300 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.	On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv or omadacycline 450 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.	On Day 1, participants received levofloxacin 750 milligrams iv. On Days 2 through 7, participants received levofloxacin 750 milligrams iv or levofloxacin 750 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.
Overall Number of Participants Analyzed	64	16	16	16	66
Measure Type: Count of Participants; Unit of Measure: Participants
	51 79.7%	15 93.8%	14 87.5%	13 81.3%	54 81.8%

4. Primary Outcome

Title	Number of Participants With No Worsening and Absence of New AP Signs and Clinical Symptoms at PTE Visit (ITT Population)
Description	Participants recorded their assessments using the mPSAQ, a 6-item questionnaire that assessed the levels of 'severity' and 'bothersomeness' for six pyelonephritis signs and symptoms. The sub-scale responses were recorded as 'did not have', 'mild', 'moderate', and 'severe' for 'severity'; and 'not at all', 'a little', 'moderately', and 'a lot' for 'bothersomeness', both scored 0-3. Total scores were calculated by summing the non-missing scores of the 6 items, divided by the number of non-missing items, and then multiplied by 6. For each sub-scale, the total score ranged from 0 (least Severe/ least bothersome) and 18 (worst severity/most bothersome). Number of participants with no worsening and absence of AP signs and clinical symptoms is reported. No worsening meant that each question score is same or better at post baseline.
Time Frame	Day 21 (A PTE occurred on Day 21 ± 2 days after the participant's first dose of study drug).

Outcome Measure Data

Analysis Population Description

The ITT population consisted of all randomized participants regardless of whether or not the participant received study drug. Participants who completed the PTE visit with evaluable data were analyzed for this end point.

Arm/Group Title	Omadacycline 200 iv/200 iv	Omadacycline 200 iv/100 iv	Omadacycline 200 iv/300 po or 100 iv	Omadacycline 200 iv/450 po or 100 iv	Levofloxacin 750 iv/750 po or iv
Arm/Group Description:	On Day 1, participants received omadacycline 200 milligrams intravenously (iv). On Days 2 through 7, participants continued to receive omadacycline 200 milligrams iv. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes.	On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes.	On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv or omadacycline 300 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.	On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv or omadacycline 450 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.	On Day 1, participants received levofloxacin 750 milligrams iv. On Days 2 through 7, participants received levofloxacin 750 milligrams iv or levofloxacin 750 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.
Overall Number of Participants Analyzed	64	16	16	16	66
Measure Type: Count of Participants; Unit of Measure: Participants
	62 96.9%	16 100.0%	16 100.0%	15 93.8%	65 98.5%

5. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events
Description	An adverse event is any untoward, undesired, or unplanned event in the form of signs, symptoms, disease, or laboratory or physiologic observations occurring in a person given a study drug or in a clinical study. A treatment-emergent adverse event was defined as any adverse event that newly appeared, increased in frequency, or worsened in severity on or after the initiation of the study drug.
Time Frame	up to approximately 28 days

Outcome Measure Data

Analysis Population Description

The Safety population consisted of all randomized participants who received at least one dose of study drug.

Arm/Group Title	Omadacycline 200 iv/200 iv	Omadacycline 200 iv/100 iv	Omadacycline 200 iv/300 po or 100 iv	Omadacycline 200 iv/450 po or 100 iv	Levofloxacin 750 iv/750 po or iv
Arm/Group Description:	On Day 1, participants received omadacycline 200 milligrams intravenously (iv). On Days 2 through 7, participants continued to receive omadacycline 200 milligrams iv. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes.	On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes.	On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv or omadacycline 300 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.	On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv or omadacycline 450 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.	On Day 1, participants received levofloxacin 750 milligrams iv. On Days 2 through 7, participants received levofloxacin 750 milligrams iv or levofloxacin 750 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.
Overall Number of Participants Analyzed	75	18	17	17	74
Measure Type: Count of Participants; Unit of Measure: Participants
Treatment Emergent Adverse Events	23 30.7%	6 33.3%	9 52.9%	8 47.1%	24 32.4%
Treatment Emergent Serious Adverse Events	0 0.0%	0 0.0%	2 11.8%	2 11.8%	2 2.7%

Adverse Events

Time Frame	Up to approximately 28 days
Adverse Event Reporting Description	The Safety Population consisted of all randomized participants who received at least one dose of study drug.
Arm/Group Title	Omadacycline 200 iv/200 iv		Omadacycline 200 iv/100 iv		Omadacycline 200 iv/300 po or 100 iv		Omadacycline 200 iv/450 po or 100 iv		Levofloxacin 750 iv/750 po or iv
Arm/Group Description	On Day 1, participants received omadacycline 200 milligrams intravenously (iv). On Days 2 through 7, participants continued to receive omadacycline 200 milligrams iv. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes.		On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes.		On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv or omadacycline 300 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.		On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv or omadacycline 450 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.		On Day 1, participants received levofloxacin 750 milligrams iv. On Days 2 through 7, participants received levofloxacin 750 milligrams iv or levofloxacin 750 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.
All-Cause Mortality
	Omadacycline 200 iv/200 iv		Omadacycline 200 iv/100 iv		Omadacycline 200 iv/300 po or 100 iv		Omadacycline 200 iv/450 po or 100 iv		Levofloxacin 750 iv/750 po or iv
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/75 (0.00%)		0/18 (0.00%)		0/17 (0.00%)		0/17 (0.00%)		0/74 (0.00%)
Serious Adverse Events
	Omadacycline 200 iv/200 iv		Omadacycline 200 iv/100 iv		Omadacycline 200 iv/300 po or 100 iv		Omadacycline 200 iv/450 po or 100 iv		Levofloxacin 750 iv/750 po or iv
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/75 (0.00%)		0/18 (0.00%)		2/17 (11.76%)		2/17 (11.76%)		2/74 (2.70%)
Blood and lymphatic system disorders
Anaemia † 1	0/75 (0.00%)	0	0/18 (0.00%)	0	0/17 (0.00%)	0	0/17 (0.00%)	0	1/74 (1.35%)	1
Gastrointestinal disorders
Duodenal ulcer haemorrhage † 1	0/75 (0.00%)	0	0/18 (0.00%)	0	0/17 (0.00%)	0	1/17 (5.88%)	1	0/74 (0.00%)	0
Infections and infestations
Renal abscess † 1	0/75 (0.00%)	0	0/18 (0.00%)	0	1/17 (5.88%)	1	0/17 (0.00%)	0	0/74 (0.00%)	0
Pyelonephritis acute † 1	0/75 (0.00%)	0	0/18 (0.00%)	0	1/17 (5.88%)	1	0/17 (0.00%)	0	0/74 (0.00%)	0
Pneumonia † 1	0/75 (0.00%)	0	0/18 (0.00%)	0	0/17 (0.00%)	0	1/17 (5.88%)	1	1/74 (1.35%)	1
Escherichia bacteraemia † 1	0/75 (0.00%)	0	0/18 (0.00%)	0	0/17 (0.00%)	0	1/17 (5.88%)	1	0/74 (0.00%)	0
1 Term from vocabulary, MedDra 20.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	2%
	Omadacycline 200 iv/200 iv		Omadacycline 200 iv/100 iv		Omadacycline 200 iv/300 po or 100 iv		Omadacycline 200 iv/450 po or 100 iv		Levofloxacin 750 iv/750 po or iv
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/75 (28.00%)		6/18 (33.33%)		7/17 (41.18%)		8/17 (47.06%)		16/74 (21.62%)
Cardiac disorders
Tachycardia † 1	0/75 (0.00%)		0/18 (0.00%)		0/17 (0.00%)		1/17 (5.88%)		0/74 (0.00%)
Gastrointestinal disorders
Diarrhoea † 1	1/75 (1.33%)		1/18 (5.56%)		0/17 (0.00%)		1/17 (5.88%)		5/74 (6.76%)
Nausea † 1	3/75 (4.00%)		0/18 (0.00%)		0/17 (0.00%)		4/17 (23.53%)		5/74 (6.76%)
Vomiting † 1	0/75 (0.00%)		0/18 (0.00%)		0/17 (0.00%)		1/17 (5.88%)		1/74 (1.35%)
General disorders
Asthenia † 1	2/75 (2.67%)		0/18 (0.00%)		0/17 (0.00%)		0/17 (0.00%)		1/74 (1.35%)
Hyperthermia † 1	0/75 (0.00%)		1/18 (5.56%)		0/17 (0.00%)		0/17 (0.00%)		0/74 (0.00%)
Infections and infestations
Asymptomatic bacteriuria † 1	3/75 (4.00%)		2/18 (11.11%)		2/17 (11.76%)		1/17 (5.88%)		1/74 (1.35%)
Oral herpes † 1	0/75 (0.00%)		0/18 (0.00%)		1/17 (5.88%)		0/17 (0.00%)		0/74 (0.00%)
Pharyngitis † 1	0/75 (0.00%)		1/18 (5.56%)		0/17 (0.00%)		0/17 (0.00%)		0/74 (0.00%)
Viral rhinitis † 1	0/75 (0.00%)		0/18 (0.00%)		1/17 (5.88%)		0/17 (0.00%)		0/74 (0.00%)
Vulvovaginal candidiasis † 1	0/75 (0.00%)		0/18 (0.00%)		1/17 (5.88%)		0/17 (0.00%)		0/74 (0.00%)
Investigations
Alanine aminotransferase increased † 1	1/75 (1.33%)		1/18 (5.56%)		0/17 (0.00%)		0/17 (0.00%)		0/74 (0.00%)
Aspartate aminotransferase increased † 1	0/75 (0.00%)		1/18 (5.56%)		0/17 (0.00%)		0/17 (0.00%)		0/74 (0.00%)
Body temperature increased † 1	0/75 (0.00%)		0/18 (0.00%)		0/17 (0.00%)		1/17 (5.88%)		1/74 (1.35%)
Gamma-glutamyltransferase increased † 1	0/75 (0.00%)		0/18 (0.00%)		0/17 (0.00%)		1/17 (5.88%)		0/74 (0.00%)
Nervous system disorders
Dizziness † 1	3/75 (4.00%)		0/18 (0.00%)		0/17 (0.00%)		0/17 (0.00%)		0/74 (0.00%)
Dysgeusia † 1	0/75 (0.00%)		0/18 (0.00%)		1/17 (5.88%)		0/17 (0.00%)		0/74 (0.00%)
Headache † 1	8/75 (10.67%)		0/18 (0.00%)		2/17 (11.76%)		3/17 (17.65%)		5/74 (6.76%)
Respiratory, thoracic and mediastinal disorders
Epistaxis † 1	0/75 (0.00%)		0/18 (0.00%)		2/17 (11.76%)		0/17 (0.00%)		0/74 (0.00%)
Skin and subcutaneous tissue disorders
Rash † 1	2/75 (2.67%)		0/18 (0.00%)		0/17 (0.00%)		0/17 (0.00%)		0/74 (0.00%)
Rash erythematous † 1	3/75 (4.00%)		0/18 (0.00%)		0/17 (0.00%)		0/17 (0.00%)		0/74 (0.00%)
Urticaria † 1	2/75 (2.67%)		0/18 (0.00%)		0/17 (0.00%)		0/17 (0.00%)		0/74 (0.00%)
Vascular disorders
Hypertension † 1	0/75 (0.00%)		0/18 (0.00%)		0/17 (0.00%)		1/17 (5.88%)		1/74 (1.35%)
1 Term from vocabulary, MedDra 20.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

In May 2019, the DMC modified the randomization algorithm based on their review of the data. After this change, participants were randomized in a 1:1 ratio to either the omadacycline 200 iv/200 iv or levofloxacin arms.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The only disclosure restriction on the Principal Investigator is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. The sponsor can request changes to the communication and require the removal of confidential information.

Results Point of Contact

• Name/Title: Paratek Medical Information
• Organization: Paratek Pharmaceuticals, Inc.
• Phone: 1-833-727-2835
• EMail: medinfo@paratekpharma.com

• Responsible Party: Paratek Pharmaceuticals Inc
• ClinicalTrials.gov Identifier: NCT03757234
• Other Study ID Numbers: PTK0796-AP-17202
• First Submitted: November 27, 2018
• First Posted: November 28, 2018
• Results First Submitted: June 8, 2020
• Results First Posted: July 7, 2020
• Last Update Posted: July 7, 2020